Efrem Lim

"Evolution and antagonism of Viperin"

I am interested in understanding the HIV viral-host interactions that occur due to the genetic conflict between host restriction factors and viral antagonists. In this proposal, I aim to identify and characterize a novel viral antagonist of Viperin, a host restriction factor that inhibits virus release. To date, a viral antagonist of Viperin has yet to be identified. This is surprising because Viperin inhibits a broad range of viruses that may include HIV-1 and is reminiscent of another restriction factor that we study called Tetherin. Although Tetherin inhibits the release of HIV-1 and other primate lentiviruses, Vpu encoded by HIV-1 was recently identified as a potent antagonist of Tetherin. Therefore, I will functionally test for viral antagonists of Viperin. This will be supported by an evolutionary analysis of primate Viperin to detect sites that were under positive selection and will be validated functionally. Using an interdisciplinary approach that integrates virology with molecular evolution, I will uncover the evolutionary history of the viral-host arms race that assaulted Viperin and the functional significance of those interactions. This research will impact our understanding of viral-host interactions.